Microbiota from healthy mice alleviates cognitive decline via reshaping the gut-brain metabolic axis in diabetic mice

Diabetic cognitive decline has been associated with the gut microbial disorders, but its potential gut-brain axis mechanisms remain unclear. Herein we transplanted the gut microbiota from healthy mice into type 1 diabetic (T1D) mice and then investigated the effect of fecal microbiota transplantation (FMT) on cognitive function and the gut-brain metabolic axis. The results demonstrate that FMT from healthy mice effectively improved the learning and memory abilities in T1D mice, and significantly reduced neuroinflammation and neuron injury in the cortex and hippocampus. Moreover, FMT partly reversed the gut microbiota and gut-brain metabolic disorders, particularly glutamate metabolism. In vitro study, we found that glutamate notably decreased microglia activation and the expression levels of proinflammatory factor. Hence, our study suggests that glutamate serves as a key signal metabolite connecting the gut to brain and affects cognitive functions.